paritaprevir/ritonavir (ABT-450/r) / AbbVie, Enanta Pharma - LARVOL DELTA

Understanding HCV Reinfection Rates in an Incarcerated Population After Cure With Interferon Free HCV Treatment (clinicaltrials.gov) - P4 | N=44 | Active, not recruiting | Sponsor: Nova Scotia Health Authority | Trial completion date: Oct 2023 ➔ Oct 2025 | Trial primary completion date: Oct 2023 ➔ Oct 2025

Trial completion date • Trial primary completion date • Hepatitis C • Hepatology • Infectious Disease • Inflammation

Understanding HCV Reinfection Rates in an Incarcerated Population After Cure With Interferon Free HCV Treatment (clinicaltrials.gov) - P4 | N=44 | Active, not recruiting | Sponsor: Lisa Barrett | Unknown status ➔ Active, not recruiting | Trial completion date: Jun 2021 ➔ Oct 2023 | Trial primary completion date: Jun 2021 ➔ Oct 2023

Enrollment closed • Trial completion date • Trial primary completion date • Hepatitis C • Hepatology • Infectious Disease • Inflammation

Resistance analysis and treatment outcomes in hepatitis C virus genotype 3 infected patients within the Italian network VIRONET-C. (PubMed, Liver Int) - "In this real-life GT3 cohort, the majority of failures harbored resistant variants carrying NS5A-RASs, the most frequent being Y93H. The presence of natural NS5A-RASs before treatment was associated with failure. Further analyses are needed to confirm this observation, particularly for the new current regimens."

Clinical • Journal • Hepatitis C Virus • Hepatology • Human Immunodeficiency Virus • Infectious Disease

Target-Centered Drug Repurposing Predictions of Human Angiotensin-Converting Enzyme 2 (ACE2) and Transmembrane Protease Serine Subtype 2 (TMPRSS2) Interacting Approved Drugs for Coronavirus Disease 2019 (COVID-19) Treatment through a Drug-Target Interaction Deep Learning Model. (PubMed, Viruses) - "Unfortunately, additional clinically significant treatment options since the approval of remdesivir are scarce...Among them, enalaprilat, an ACE inhibitor, showed a K value of 1.5 nM against the ACE2. Furthermore, three of the top 30 drugs with strong affinity prediction for the TMPRSS2 are anti-hepatitis C virus (HCV) drugs, including ombitasvir, daclatasvir, and paritaprevir. Notably, of the top 30 drugs, AT1R blocker eprosartan and neuropsychiatric drug lisuride showed similar gene expression profiles to potential TMPRSS2 inhibitors. Collectively, we suggest that drugs predicted to have strong inhibitory potencies to ACE2 and TMPRSS2 through the DTI model should be considered as potential drug repurposing candidates for COVID-19."

Journal • Hepatitis C Virus • Hepatology • Infectious Disease • Novel Coronavirus Disease • Psychiatry • Respiratory Diseases • TMPRSS2

The potential of Paritaprevir and Emetine as inhibitors of SARS-CoV-2 RdRp. (PubMed, Saudi J Biol Sci) - "The recent elucidation of the experimental structure of SARS-CoV-2 RdRp enzyme complexed with triphosphate form of Remdesivir (RTP) has opened an avenue for structure-based identification of potent inhibitors...The top 3 hits among the FDA approved drugs were Paritaprevir (D33), Rilpivirine (D19) and Simeprevir (D31) which scored binding energies between -8.08 kcal/mol and -10.46 kcal/mol...Further, the physicochemical properties of the molecules were evaluated. These identified potential inhibitors warrant further experimental investigations before their acceptance as drug candidates for the treatment of the disease."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

[VIRTUAL] OUTCOMES OF HEPATITIS C TREATMENT ARE SIMILAR IN CANADIAN INDIGENOUS PEOPLE COMPARED TO NON-INDIGENOUS PATIENTS (AASLD 2020) - "Other regimens included sofosbuvir+ledipasvir, sofosbuvir+daclatasvir and paritaprevir+ombitasvir+dasabuvir)...There were 5 patients who did not achieve SVR; 2 were treated with sofosbuvir+ledipasvir, 1 with elbasvir+grazoprevir, 1 with sofosbuvir+velpatasvir and 1 with sofosbuvir+daclatasvir... Indigenous patients with reported SVR were younger and more likely to be female. Importantly, DAA SVR rates were comparable to the non-indigenous control group. These real-world effectiveness data add to the limited global data on DAA effectiveness in Indigenous people, and suggests DAA-based HCV microelimination in Indigenous people is possible."

Clinical • Hepatitis C Virus • Hepatology • Infectious Disease

The effect of anemia on the efficacy and safety of treating chronic hepatitis C infection with direct-acting antivirals in patients with chronic kidney disease. (PubMed, Int Urol Nephrol) - "Hemoglobin levels of < 10.5 g/dL prior to DAA treatment did not affect the virological response in renal patients but was associated with increased serum creatinine among KTx and those with CKD."

Clinical • Journal • Acute Kidney Injury • Anemia • Chronic Kidney Disease • Hematological Disorders • Hepatitis C Virus • Hepatology • Infectious Disease • Nephrology • Renal Disease • Transplantation

Effectiveness and safety of IFN-free DAA HCV therapy in HIV/HCV co-infected persons: Results from a pan-European study. (PubMed, J Acquir Immune Defic Syndr) - "Our findings from real-world data on HIV/HCV co-infected individuals across Europe show DAA treatment is well tolerated, and that high rates of SVR12 can be achieved in all regions of Europe."

Clinical • Journal • Hepatitis C Virus • Human Immunodeficiency Virus • Infectious Disease

Hepatitis C therapy with direct antiviral agents in patients with advanced chronic kidney disease: real-world experience of the German Hepatitis C-Registry (Deutsches Hepatitis C-Register). (PubMed, Eur J Gastroenterol Hepatol) - "Different DAA therapies can be safely used with high sustained virological response rates in patients with GFR less than 30 ml/min. Ribavirin has to be avoided because of poor tolerability."

Clinical • Journal • Real-World Evidence • Chronic Kidney Disease • Hepatitis C Virus • Hepatology • Infectious Disease • Nephrology • Renal Disease

Direct antiviral therapy for treatment of hepatitis C: A real-world study from Brazil. (PubMed, Ann Hepatol) - "SOF-based DAA regimens are effective and safe in the heterogeneous highly admixed Brazilian population and could remain an option for HCV treatment at least in low-income countries."

Clinical • Journal • Real-World Evidence • Fibrosis • Hepatitis C Virus • Hepatology • Immunology • Infectious Disease

Development and Validation of a New LC-MS/MS Analytical Method for Direct-Acting Antivirals and Its Application in End-Stage Renal Disease Patients. (PubMed, Eur J Drug Metab Pharmacokinet) - "An efficient analytical method for the determination of DAAs is presented. The method overcomes the potential analytical response fluctuation in ESRD. The developed method show improved extraction recoveries and is suitable for routine application in developing economies where hepatitis C virus is most prevalent."

Clinical • Journal • Chronic Kidney Disease • Hepatitis C Virus • Hepatology • Infectious Disease • Nephrology • Renal Disease

HCV genotype 1-6 NS3 residue 80 substitutions impact protease inhibitor activity and promote viral escape. (PubMed, J Hepatol) - "Position-80-substitutions had relatively low fitness cost and the potential to promote HCV escape from clinically relevant PIs in vitro, despite minor impact in classical short-term resistance assays."

Journal • Hepatitis C Virus • Hepatology

In silico structure modelling of SARS-CoV-2 Nsp13 helicase and Nsp14 and repurposing of FDA approved antiviral drugs as dual inhibitors. (PubMed, Gene Rep) - "Simeprevir (SMV), Paritaprevir (PTV) and Grazoprevir (GZR) were the common leads identified which show higher binding affinity to both nsp13 helicase and nsp14 as compared to the control inhibitors and therefore, they might be potential dual-target inhibitors. The leads also establish a network of hydrogen bonds and hydrophobic interactions with the key residues lining the active site pockets. The present findings suggest that these FDA approved antiviral drugs can be subjected to repurposing against SARS-CoV-2 infection after verifying the in silico results through in vitro and in vivo studies."

FDA event • Journal • Infectious Disease • Novel Coronavirus Disease

Identification of promising antiviral drug candidates against non-structural protein 15 (NSP15) from SARS-CoV-2: an in silico assisted drug-repurposing study. (PubMed, J Biomol Struct Dyn) - "Taken together, we propose that Simeprevir and Paritaprevir are promising drug candidates to inhibit NSP15 and may act as potential therapeutic agents against SARS-CoV-2. Communicated by Ramaswamy H. Sarma."

Journal • Infectious Disease • Novel Coronavirus Disease

[VIRTUAL] Resistance and phylogenetic analysis in HCV-2c infected patients within the Italian network VIRONET-C (EASL-ILC-I 2020) - "84 DAA-naïve pts with SVR and 40 DAA-failed with GT2c infection were treated with the following recommended sofosbuvir(SOF)/velpatasvir (VEL)±ribavirin for misclassified genotype were Paritaprevir/r+Ombitasvir+Dasabuvir±RBV (N=0/3), grazoprevir/elbasvir (N=0/2). In this large Italian cohort of GT2 infected pts, the most prevalent subtype was the unusual subtype c. The majority of GT2c failures with recommended regimens did not show specific HCV RAS at failure. Further structural and phenotypic analyses should investigate the role of the common polymorphisms observed in GT2c."

Clinical • Hepatitis C Virus

Drug repurposing using computational methods to identify therapeutic options for COVID-19. (PubMed, J Diabetes Metab Disord) - "According to the results, glecaprevir, paritaprevir, simeprevir, ledipasvir, glycyrrhizic acid, TMC-310911, and hesperidin showed highly favorably free binding energies with all tested target proteins. The above-mentioned drugs can be regarded as candidates to treat COVID-19 infections, but further study on the efficiency of these drugs is also necessary."

Journal • Infectious Disease • Novel Coronavirus Disease • TMPRSS2

Structure-based virtual screening of phytochemicals and repurposing of FDA approved antiviral drugs unravels lead molecules as potential inhibitors of coronavirus 3C-like protease enzyme. (PubMed, J King Saud Univ Sci) - "A few promising leads with dual inhibition potential were identified among FDA approved antiviral drugs which include DB13879 (Glecaprevir), DB09102 (Daclatasvir), molecule DB09297 (Paritaprevir) and DB01072 (Atazanavir). Among the phytochemicals, 11,646,359 (Vincapusine), 120,716 (Alloyohimbine) and 10,308,017 (Gummadiol) showed triple inhibition potential against all the three targets and 102,004,710 (18-Hydroxy-3-epi-alpha-yohimbine) exhibited dual inhibition potential. Hence, the proposed lead molecules from our findings can be further investigated through in vitro and in vivo studies to develop into potential drug candidates against human coronaviral infections."

FDA event • Journal • Infectious Disease • Novel Coronavirus Disease

Features of resistance-associated substitutions after failure of multiple direct-acting antiviral regimens for hepatitis C. (PubMed, JHEP Rep) - "Among patients with failure of 1 regimen, Y56H and D168V in NS3 were more frequently detected after failure of paritaprevir, whereas D168E was more frequently detected after failure of regimens including asunaprevir. R30H and L31-RAS in NS5A were frequently detected after failure of regimens including daclatasvir...S282T RAS in NS5B was detected in 3.9% of ledipasvir/sofosbuvir failures...We investigated RASs after failure of various treatments for chronic hepatitis C, and found that more complicated RASs accumulated in the viral genome with successive failed treatments. The highly resistant P32del RAS at NS5A region was uniquely found in patients for whom DAA treatments had failed, and was linked to the presence and absence of specific RASs."

Journal • Fibrosis • Hepatitis C Virus • Hepatology • Immunology • Infectious Disease

A Follow up Study Designed to Obtain Long Term Data on Subjects Who Either Achieved a Sustained Virologic Response or or Did Not Achieve a Sustained Virologic Response in an Abbott Sponsored Hepatitis C Study (clinicaltrials.gov) - P3; N=500; Active, not recruiting; Sponsor: AbbVie (prior sponsor, Abbott); Enrolling by invitation -> Active, not recruiting

Enrollment closed • Biosimilar • Hepatitis C Virus • Immunology • Inflammation

Impact of IL28B gene polymorphism on efficacy and safety of direct acting antivirals in hepatitis C Egyptian patients. (PubMed, Int J Clin Pharm) - "Patients were randomized into two groups, group 1 received sofosbuvir plus daclatasvir and group 2 received paritaprevir, ombitasvir and ritonavir plus ribavirin. Conclusion CT genotype is the predominant genotype in easy to treat HCV Egyptian patients. IL28B genotypes hasn't any predictive value on the efficacy or the safety of direct acting antiviral regimens."

Clinical • Journal • Fibrosis • Gastroenterology • Gastrointestinal Cancer • Hepatitis C Virus • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Liver Cirrhosis • Oncology • Solid Tumor

Interferon-free Therapy as the Cause of White Matter Tracts and Cerebral Perfusion Recovery in Patients with Chronic Hepatitis C. (PubMed, J Viral Hepat) - "In HCV-positive patients therapy with ombitasvir, paritaprevir boosted with ritonavir and dasabuvir, with or without ribavirin, was scheduled. Liver fibrosis regression in elastography, APRI and improvement in cognitive tests were observed. This is the first report of interferon-free therapy as the cause of white matter tracts recovery as well as cerebral perfusion improvement in HCV-infected patients, indicating better functioning of frontal lobes after interferon-free treatment."

Clinical • Journal • Fibrosis • Hepatitis C Virus • Immunology • Infectious Disease

Pre-existing resistance associated polymorphisms to NS3 protease inhibitors in treatment naïve HCV positive Pakistani patients. (PubMed, PLoS One) - "All these substitutions were associated with Boceprevir, Simeprevir, Telaprevir, and Paritaprevir. Natural RAPs are common in chronic HCV patients infected with genotype 1a, 3a and 3b, the most prevalent subtypes in Pakistan. High prevalence of HCV NS3 RAPs suggested a large scale study of the NS3 gene before the introduction of NS3 protease inhibitors in Pakistan."

Clinical • Journal • Hepatitis C Virus • Infectious Disease

MANAGEMENT OF HEPATITIS C RELATED MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS IN THE ERA OF DIRECT ANTIVIRAL AGENTS (ERA-EDTA 2018) - "...Kidney biopsy revealed MPGN with fibrocellular crescents.She started 3 days methyl prednisolone 500 mg/d, then prednisone 60 mg/day...Monthly IV cyclophosphamide (800 mg) was added. DAA therapy was started with Sofosbuvir, Daclatasvir and ribavirine (RBV) (200 mg bd), and due to declining hemoglobin, RBV was discontinued after 3w.Case 2:62 year old female presented with extensive vasculitic eruption, pallor and deterioration of kidney functions...Thus the previous dose was resumed.6 months after starting IS, she started DAA: ombitasvir, paritaprevir and ritonavir®(Qurevo 2 tablets/d), and RBV (200 mg/d) which was discontinued after 2m. After 12 weeks of DAA therapy, both patients achieved SVR indicated by undetectable viral RNA... Management of HCV related MPGN should be tailored according to the clinical severity and response to therapy. Both cases had a relapse. While case 1 relapsed after achieving partial remission and SVR, thus hindering successfu

Biosimilar • Complement-mediated Rare Disorders • Dermatology • Hepatitis C Virus • Immunology • Renal Disease • Rheumatoid Arthritis • Venous Thromboembolism

Efficacy of direct acting antivirals: UK real world data from a well characterised predominantly cirrhotic HCV cohort. (PubMed, J Med Virol) - "DAA regimens utilised: genotype1 sofosbuvir (SOF)/Ledipasvir/±Ribavirin (625/900, 69%) and Ombitasvir/Paritaprevir/Dasabuvir/±RBV (220/900, 24%), and in genotype 3 SOF/Daclatasvir + RBV (256/455, 56%) and SOF/pegylated interferon/RBV (157/455, 35%). This real world UK data, comprising of a predominantly cirrhotic HCV genotype 1/3 cohort, confirms DAA efficacy with an overall 91% SVR12, with 51% recompensating post treatment. Genotype 3 infection was a predictor of treatment failure."

Clinical • Journal • Real-World Evidence • Fibrosis • Hepatitis C Virus • Hepatology • Immunology • Infectious Disease

Evolutionary Pathways to Persistence of Highly Fit and Resistant Hepatitis C Virus Protease Inhibitor Escape Variants. (PubMed, Hepatology) - "The developed genotype 1, 2, and 3 variants with persistent 156-RASs had exceptionally high fitness and resistance to grazoprevir, paritaprevir, glecaprevir, and voxilaprevir. A156T dominated in genotype 1 glecaprevir and voxilaprevir escape variants, and pre-existing A156T facilitated genotype 1 escape from clinically relevant combination treatments with grazoprevir/elbasvir and glecaprevir/pibrentasvir... Comprehensive PI resistance profiling for HCV genotypes 1-6 revealed 156-RASs as key determinants of high-level resistance across clinically relevant PIs. We obtained in vitro proof-of-concept for persistence of highly fit genotype 1-3 156-variants, which might pose a threat to clinically relevant combination treatments."

Journal • Hepatitis C Virus • Infectious Disease